Proportions of acetyl-histone-positive hepatocytes indicate the functional status and prognosis of cirrhotic patients

World J Gastroenterol. 2015 Jun 7;21(21):6665-74. doi: 10.3748/wjg.v21.i21.6665.

Abstract

Aim: To investigate whether the proportions of acetyl-histone-positive hepatocytes could be used as markers of deteriorating liver function.

Methods: In total, 611 cirrhotic cases from 3701 patients who were diagnosed during the past 15 years were screened, and 152 follow-up cases were selected. Paraffin tissue microarray was prepared for immunohistochemistry to examine acetyl-histone expression. The proportions of positive hepatocytes were recorded, and their correlations to clinical and laboratory indicators were analyzed statistically.

Results: The proportions of H2AK5ac(+), H3K9/K14ac(+) and H3K27ac(+) hepatocytes gradually increased with deteriorating liver function and with increasing levels of serum markers of liver injury. In the follow-up cases, patients with > 70% H2AK5ac(+), H3K9/K14ac(+) or H3K27ac(+) hepatocytes had statistically lower survival rates (P < 0.05). Furthermore, > 70% H2AK5ac(+) or H3K27ac(+) hepatocytes were strong independent predictors of overall survival (P < 0.05).

Conclusion: The proportions of acetyl-histone-positive hepatocytes are closely associated with the liver function and prognosis of cirrhotic patients.

Keywords: Cirrhosis; Histone acetylation; Liver function; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / analysis
  • Biopsy
  • Child
  • Female
  • Hepatocytes / chemistry*
  • Hepatocytes / pathology
  • Histones / analysis*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Liver / chemistry*
  • Liver / pathology
  • Liver Cirrhosis / diagnosis*
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / mortality
  • Liver Cirrhosis / pathology
  • Liver Function Tests*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Severity of Illness Index
  • Tissue Array Analysis
  • Young Adult

Substances

  • Biomarkers
  • Histones